Genetic counseling: 22q11 Deletion Syndrome
22q11 Deletion Syndrome (a.k.a. Velocardiofacial Syndrome (VCF), DiGeorge Syndrome) Diagnosis *Caused by a deletion of material from one copy of the long arm of chromosome 22 **Submicroscopic deletion in DiGeorge Chromosomal Region (DGCR) **Chromosome banding may sometimes detect deletion **FISH testing detects deletion in 95% of affected individuals *Autosomal dominant inheritance **About 94% of patients have de novo mutation **Parents of affected individuals should have FISH testing ***Offspring of affected individual have 50% chance of inheriting 22q11 deletion ***Recurrence risk for siblings of affected individual is very small if FISH testing shows the parents do not have the deletion *Several genes are located within the DGCR **Some of these gene products have been identified **Cannot predict genotype-phenotype correlation because size of deletion does not seem to correlate with severity of characteristics Characteristic Findings: *Congenital heart disease **Found in about 74% of affected individuals **Usually conotruncal malformations ***Teratology of Fallot ***Interrupted aortic arch ***Truncus arteriosis ***Ventricular septal defect (VSD) **Conotruncal malformations identified in infancy/early childhood and can be surgically repaired **Mild problems with the aorta may not be recognized *Palatal abnormalitites **Found in about 69% of affected individuals **Several types of abnormalities observed ***Velopharyngeal incompetance (VPI) ***Submucosal cleft palate ***Visible cleft palate ***Cleft lip and palate ***Bifid uvulae **May be surgically repaired **May affect speech development **Speech therapy is recommended *Feeding difficulties **Found in about 30% of affected individuals **May be due to palate or heart problems **May also be caused by problems transporting food from the mouth to the esophagus **Signs of feeding difficulty ***Infants are irritable, gag, vomit, have a weak suck ***Younger children find spoon feeding easier but have trouble drinking from a cup ***Older children have difficulty with lumpy, crunchy foods **May be treated by teaching children better feeding practices *Immunodeficiency **Caused by small or missing thymus gland **Causes greatest number of problems in first year of life **Children may have frequent infections such as bronchitis or pneumonia **As children grow older, T cell production improves *Hypoparathyroidism **Regulates calcium levels in bloodstream ***Absence or underdevelopment leads to hypocalcemia ***May cause tremors, seizures, muscle spasms, abnormal breathing, and abnormal heart rhythms **Diagnosed by a blood test **Treated with calcium supplements *Growth hormone deficiency **Approximately 41% of affected individuals are below the 5th percentile in height **May be caused by abnormalities in formation of pituitary gland ***In only about 1/10 of individuals with 22q11 deletion ***Causes reduced levels of growth factors **Can be determined with a blood test **Treatment with injections of growth hormones *Characteristic Facial Features **Nose - bulbous nasal tip, prominent nasal root, nasal dimple **Ear - overfolded helices; cupped, microtic, and protuberant ears; narrow external auditory meati **Eyes - hooding of upper or lower lid, ptosis, epicanthal folds *Renal anomalies **Found in about 37% of affected individuals **Includes single kidney, echogenic kidney, small kidneys, and other renal anomalies *Juvenile rheumatiod arthiritis (JRA) **About 150 times more frequent than in general population **Age of onset is 17 months to 5 years *Developmental difficulties **Found in 70-90% of affected individuals **Development of motor skills ***Due to problems with muscle strength and coordination ***Often delayed in sitting, crawling, walking ***May be helped by physical therapy *Learning **Typically have slower learning rate **Follow same learning sequence as other children but at slower pace **Often have strong verbal skills but weaker math skills **May have difficulty paying attention **Early diagnosis and intervention important **May require learning support *Speech and language **Verbal speech usually does not develop until 2-3 years **May also have difficulty in formation of sounds **Palatal problems often lead speech problems **Early intervention by speech and language pathologist is important *Behavioral difficulties **About 40% of affected individuals develop psychiatric illness ***Depression ***Anxiety ***Schizophrenia ***Bipolar disorders **May be evident as tantrums and mood swings in childhood **Social skills training and counseling may be necessary Resources *Cincinnati Velocardiofacial Support Group :Teresa Paul :9327 Bluewing Terrace :Cincinnati, Ohio 45236 :Email: MOTHERTP@aol.com *Velo-Cardio-Facial Syndrome Education Foundation :Jacobson hall Room 707 :University Hospital :750 East AdamsStreet :Syracuse, NY 13210 :Phone: 315-464-6590 :Email: vcfsef@hscsyr.edu :Web: http://www.vcfsef.org *International DiGeorge/VCF Support Network :c/o Family Vioces of New York :461/2 Clinton Avenue :Cortland, NY 13045 :Phone: 607-753-1621 (day) 607-753-1250 (evening) *Chromosome Deletion Outreach, Inc. :PO Box 724 :Boca Raton, FL 33429-0724 :Phone: 561-395-4252 :Email: cdo@worldnet.att.net :Web: http://members.aol.com/cdousa/cdo.hem References *The Children's Hospital of Philadelphia. Faces of Sunshine: The 22q11.2 Deletion. *NIH Gene Clinics web site: http://www.geneclinics.org/profiles/22q11deletion/details.html *OMIM: http://www.ncbi.nlm.nin.gov/htbin-post/Omim/dispmim?192430 *Smith's. Shprintzen Syndrome. Notes The information in this outline was last updated in 2002. Material obtained under GFDL Licence from http://en.wikibooks.org/wiki/Handbook_of_Genetic_Counseling